It has been established that the medial temporal lobe, including the hippocampus, is crucial for associative memory. The aim of the current functional magnetic resonance imaging (fMRI) study was to investigate whether the hippocampus is differentially activated for associations between items processed in the same neocortical region (within-domain) as compared with associations between items processed in different neocortical regions (between-domain). Here, we show that the hippocampus is significantly more active for between-domain associations compared with within-domain associations. Thus, the hippocampus is important for associative encoding, and furthermore, shows greater activation when the stimuli to be associated come from different stimulus categories.